Inhibition of Leukotriene Production by N-[4-[4-(Diphenylmethyl)-1-piperazinyl]butyl]-3-(6-methyl-3-pyridyl) Acrylamide (AL-3264), a New Antiallergic Agent

摘要

References(26) Cited-By(2) The effects of AL-3264, which exhibits a 5-lipoxygenase (5-LO) inhibiting property by blocking histamine H1-receptors and inhibition of histamine release, were examined on leukotriene (LT) production and LT-mediated responses. AL-3264 (1-30 μM) inhibited the A23, 187-induced LT production from human leukocytes with almost the same potency as that of nordihydroguaiaretic acid. AL-3264 (30-100 mg/kg, p.o.) inhibited the antigen-induced LT production in the abdominal cavity of passively sensitized rats; its effect was as potent as that of AA-861, a 5-LO inhibitor. AL-3264 (30 μM) suppressed both the initial and sustained phases of the antigen-induced contractions in isolated trachea from actively sensitized guinea pig. Phenidone (3 μM), a dual inhibitor of 5-LO and cyclooxygenase (CO), suppressed the sustained phase, while indomethacin was without effect on either phase. AL-3264 (40-160 mg/kg, p.o.) suppressed the arachidonic acid-induced ear edema in mice, for which 5-LO inhibitors were effective but antihistamines were not. The anti-edematous effect of AL-3264 (160 mg/kg) was reduced by intradermal administration of LTC4 (0.1 μg). These results suggest that AL-3264 suppresses LT production in vivo and in vitro by inhibiting 5-LO activity, and this property may contribute to the antiallergic effect of AL-3264.